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TNP-470 inhibits growth and the production of vascular endothelial growth factor of uterine carcinosarcoma cells in vitro.

AbstractBACKGROUND:
Carcinosarcoma is the most aggressive neoplasm among the known uterine malignancies. Most patients who are affected with this biphasic neoplasm hardly show any response to common anti-cancer drugs or radiotherapy and thus they tend to show an extremely poor prognosis. This is the first study to examine the inhibitory and anti-angiogenic effects of angiogenesis inhibitor TNP-470, a synthetic analogue of fumagillin, for human uterine carcinosarcoma in vitro.
MATERIALS AND METHODS:
The direct growth-inhibitory effect of TNP-470 was examined by an MTT assay in vitro. The levels of vascular endothelial growth factor (VEGF) in the culture supernate of TNP-470 treated FU-MMT-1 cells were also analyzed by an enzyme-linked immunosorbent assay (ELISA). The VEGF expression of TNP-470 treated FU-MMT-1 cells was also immunohistochemically examined using an anti-VEGF antibody.
RESULTS:
TNP-470 inhibited the growth of FU-MMT-1 cells in vitro. The level of VEGF in the culture supernatant of TNP-470 treated FU-MMT-1 cells was significantly lower than that of the control (TNP-470 untreated FU-MMT-1 cells) in vivo. The expression of VEGF in TNP-470 treated FU-MMT-1 cells immunocytochemically decreased in comparison to that of the control TNP-470 untreated FU-MMT-1 cells).
CONCLUSIONS:
Our in vitro findings suggest that this angiogenesis inhibitor, TNP-470, might be a novel therapeutic agent for uterine carcinosarcoma. However, further in vivo experimental studies using TNP-470 for this tumor will be necessary before any definitive conclusions can be made.
AuthorsM Emoto, M Ishiguro, H Iwasaki, M Kikuchi, T Kawarabayashi
JournalAnticancer research (Anticancer Res) 2000 Jan-Feb Vol. 20 Issue 1C Pg. 601-4 ISSN: 0250-7005 [Print] GREECE
PMID10769702 (Publication Type: Journal Article)
Chemical References
  • Antibiotics, Antineoplastic
  • Culture Media
  • Cyclohexanes
  • Endothelial Growth Factors
  • Lymphokines
  • Sesquiterpenes
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • O-(chloroacetylcarbamoyl)fumagillol
Topics
  • Antibiotics, Antineoplastic (pharmacology)
  • Carcinosarcoma (metabolism, pathology)
  • Cell Division (drug effects)
  • Culture Media
  • Cyclohexanes
  • Endothelial Growth Factors (biosynthesis, metabolism)
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphokines (biosynthesis, metabolism)
  • Sesquiterpenes (pharmacology)
  • Tumor Cells, Cultured
  • Uterine Neoplasms (metabolism, pathology)
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

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